1. Field of the Invention
The present invention is concerned with the screening for the presence of drugs in fluid samples. More particularly, the present invention is concerned with screening for the presence of drugs in fluid samples which may or may not contain any drugs being screened for. Still more particularly, the present invention is concerned with the screening for the presence of drugs in fluid samples when it is known that the individual providing the fluid sample is on drugs and the screening procedure can help determine proper medication levels. In the instance where it is not known whether or not the individual providing the sample is on any drugs, the present invention is particularly useful in that it identifies the presence of drug families rather than discreet drugs. The same is true for when it is known that the individual providing the sample is supposed to be on a drug that is in a particular family of drugs whereby the screening procedures can be used to determine compliance with taking prescribed medications. Even more particularly, the present invention utilizes a screening technique which identifies the presence of at least one member of a family of drugs by the effects of the drugs on specific enzymes or receptors which are acted upon by the specific families of drugs.
2. Description of the Prior Art
The laboratory screening of drugs, both prescription and non-prescription, is typically by a form of immunodetection which relies on the development of a specific antibody to the drug or compound being screened for. This antibody is then used to detect the drug in a sample which may or may not contain the drug or compound of interest. A major hurdle which needs to be overcome to accomplish immunodetection using this method is the development of an antibody that is specific for each drug. The antibody must be produced with a sufficient titer, a measure of concentration, to efficiently detect the presence of the drug. Additionally, the antibody must have sufficient specificity to react only with the drug of interest so that accurate results may be obtained. While these requirements are normally obtainable, they inherently result in a system with severe limitations. The greatest of these limitations is the detection of the drug after it is no longer biologically active.
Drugs may be broadly classified into one of two categories. The first type of drug is active in the form that is present in the drug as taken by an individual. This category of drugs requires no structural modification and the drugs in this class are therapeutically active in the medication. The second category of drugs requires a structural change before becoming therapeutically active. In both categories, additional metabolites may also be as active as the parent compound or its first metabolite while other metabolites may have little or no activity. This drastically increases the difficulty in determining the amount of therapeutically active drug present in any fluid sample taken from an individual. Due to the similarity of metabolite structures with the drug as taken or with other metabolites, the metabolites may also contribute to the immunodetection signal so that, regardless of prodrug or metabolite, the signal would be related to total drug exposure. In some instances a metabolite may be therapeutically inactive while still being detected by the antibody developed to detect the drug. In this scenario, immunological detection would overestimate the concentration of active drug present. The opposite problem may occur where a detected metabolite has an even greater activity than the parent drug. In this scenario, immunological detection would underestimate the concentration of active drug present. Thus, current immunodetection methods cannot differentiate the biological activity of the drug or its metabolites. The result is a system which is good at detection of the presence of a drug but totally ineffective at the more important determination of the amount of active drug present. Moreover, metabolites which are similar in structure, regardless of their activity level, may also be identified and thereby further contribute to an inaccurate determination of the concentration of active drug present in the sample tested. Accordingly, one thing needed in the art is a drug screening test which only determines or detects the presence or levels of active drugs in fluid samples.
Many drugs and classes of drugs produce their effect by activational inhibition of specific receptors or activation or inhibition of specific enzymes. Often, an entire class of drugs will produce the same effect on a specific receptor or enzyme, thereby resulting in the therapeutic effect. In the case of drugs and classes of drugs effecting receptors, a drug may bind to a receptor site, thereby inhibiting the binding of the natural activators or inhibitors. Alternatively, the drug may react in the receptor site and irreversibly modify the structure or shape of the receptor, thereby resulting in its inactivation. Other methods of inhibition include binding to other regulatory sites present on the receptor, interfering with cofactor binding, or interaction with other cell surface molecules required for receptor action. Irrespective of the method of inactivation or inhibition, the receptor no longer works with its normal efficiency. Accordingly, another thing needed in the art is a drug screening test which identifies drug presence by determining effects on specific receptors. The usefulness of such a test could be greatly increased if the test could identify the presence of a class of drugs regardless of which specific drug in that class was actually present.
In the case of drugs which effect the activation or inhibition of specific enzymes, a drug may bind to an enzyme's catalytic site and inhibit the binding of the natural substrate. Alternatively, the drug may react in the catalytic site and irreversibly modify the enzyme, thereby resulting in its inactivation. Other methods of inhibition include binding to the regulatory sites present on the enzyme, interfering with cofactor binding, or interaction with the normal substrate, thereby limiting its binding to the enzyme. Irrespective of the method of inactivation or inhibition, the enzyme no longer works with its normal efficiency. In reality, the drug and/or its metabolites have reduced the enzyme's catalytic rate. Therefore, another thing needed in the art is a drug screening test which identifies drug presence by determining enzyme activity. Again, the usefulness of such a test could be greatly increased if the test could identify the presence of an entire class of drugs, regardless of which specific drug in that class was actually present.